Leak signature space: an original representation for robust leak location in water distribution networks

In this paper, an original model-based scheme for leak location using pressure sensors in water distribution networks is introduced. The proposed approach is based on a new representation called the Leak Signature Space (LSS) that associates a specific signature to each leak location being minimally affected by leak magnitude. The LSS considers a linear model approximation of the relation between pressure residuals and leaks that is projected onto a selected hyperplane. This new approach allows to infer the location of a given leak by comparing the position of its signature with other leak signatures. Moreover, two ways of improving the method's robustness are proposed. First, by associating a domain of influence to each signature and second, through a time horizon analysis. The efficiency of the method is highlighted by means of a real network using several scenarios involving different number of sensors and considering the presence of noise in the measurements.Postprint (published version

Dynamics of alternative modes of RNA replication for positive-sense RNA viruses

[EN] We propose and study nonlinear mathematical models describing the intracellular time dynamics of viral RNA accumulation for positive-sense single-stranded RNA viruses. Our models consider different replication modes ranging between two extremes represented by the geometric replication (GR) and the linear stamping machine replication (SMR). We first analyse a model that quantitatively reproduced experimental data for the accumulation dynamics of both polarities of turnip mosaic potyvirus RNAs. We identify a non-degenerate transcritical bifurcation governing the extinction of both strands depending on three key parameters: the mode of replication (a), the replication rate (r) and the degradation rate (d) of viral strands. Our results indicate that the bifurcation associated with a generically takes place when the replication mode is closer to the SMR, thus suggesting that GR may provide viral strands with an increased robustness against degradation. This transcritical bifurcation, which is responsible for the switching from an active to an absorbing regime, suggests a smooth (i.e. secondorder), absorbing-state phase transition. Finally, we also analyse a simplified model that only incorporates asymmetry in replication tied to differential replication modes.This work was funded by the Human Frontier Science Program Organization grant RGP12/2008, by the Spanish Ministerio de Ciencia e Innovacion grants BIO2008-01986 (J.A.D.) and BFU2009-06993 (S.F.E.) and by the Santa Fe Institute. F. M. is the recipient of a predoctoral fellowship from Universitat Politecnica de Valencia. We also thank the hospitality and support of the Kavli Institute for Theoretical Physics (University of California at Santa Barbara), where part of this work was developed (grant NSF PHY05-51164).Sardanyes Cayuela, J.; Martinez, F.; Daros Arnau, JA.; Elena Fito, SF. (2012). Dynamics of alternative modes of RNA replication for positive-sense RNA viruses. Journal of the Royal Society. Interface. 9(69):768-776. https://doi.org/10.1098/rsif.2011.0471S768776969Endy, D., Kong, D., & Yin, J. (1997). Intracellular kinetics of a growing virus: A genetically structured simulation for bacteriophage T7. Biotechnology and Bioengineering, 55(2), 375-389. doi:10.1002/(sici)1097-0290(19970720)55:23.0.co;2-gYou, L., Suthers, P. F., & Yin, J. (2002). Effects of Escherichia coli Physiology on Growth of Phage T7 In Vivo and In Silico. Journal of Bacteriology, 184(7), 1888-1894. doi:10.1128/jb.184.7.1888-1894.2002Reddy, B., & Yin, J. (1999). Quantitative Intracellular Kinetics of HIV Type 1. AIDS Research and Human Retroviruses, 15(3), 273-283. doi:10.1089/088922299311457Dahari, H., Ribeiro, R. M., Rice, C. M., & Perelson, A. S. (2006). Mathematical Modeling of Subgenomic Hepatitis C Virus Replication in Huh-7 Cells. Journal of Virology, 81(2), 750-760. doi:10.1128/jvi.01304-06Sidorenko, Y., & Reichl, U. (2004). Structured model of influenza virus replication in MDCK cells. Biotechnology and Bioengineering, 88(1), 1-14. doi:10.1002/bit.20096Lim, K., Lang, T., Lam, V., & Yin, J. (2006). Model-Based Design of Growth-Attenuated Viruses. PLoS Computational Biology, 2(9), e116. doi:10.1371/journal.pcbi.0020116Eigen, M., McCaskill, J., & Schuster, P. (2007). The Molecular Quasi-Species. Advances in Chemical Physics, 149-263. doi:10.1002/9780470141243.ch4Krakauer, D. C., & Komarova, N. L. (2003). Levels of selection in positive-strand virus dynamics. Journal of Evolutionary Biology, 16(1), 64-73. doi:10.1046/j.1420-9101.2003.00481.xSRIVASTAVA, R., YOU, L., SUMMERS, J., & YIN, J. (2002). Stochastic vs. Deterministic Modeling of Intracellular Viral Kinetics. Journal of Theoretical Biology, 218(3), 309-321. doi:10.1006/jtbi.2002.3078Zhdanov, V. P. (2004). Bifurcation in a generic model of intracellular viral kinetics. Journal of Physics A: Mathematical and General, 37(5), L63-L66. doi:10.1088/0305-4470/37/5/l03Domingo, E., Sabo, D., Taniguchi, T., & Weissmann, C. (1978). Nucleotide sequence heterogeneity of an RNA phage population. Cell, 13(4), 735-744. doi:10.1016/0092-8674(78)90223-4Sanjuan, R., Nebot, M. R., Chirico, N., Mansky, L. M., & Belshaw, R. (2010). Viral Mutation Rates. Journal of Virology, 84(19), 9733-9748. doi:10.1128/jvi.00694-10MANRUBIA, S., & LAZARO, E. (2006). Viral evolution. Physics of Life Reviews, 3(2), 65-92. doi:10.1016/j.plrev.2005.11.002Sardanyes, J., Sole, R. V., & Elena, S. F. (2009). Replication Mode and Landscape Topology Differentially Affect RNA Virus Mutational Load and Robustness. Journal of Virology, 83(23), 12579-12589. doi:10.1128/jvi.00767-09Thébaud, G., Chadœuf, J., Morelli, M. J., McCauley, J. W., & Haydon, D. T. (2009). The relationship between mutation frequency and replication strategy in positive-sense single-stranded RNA viruses. Proceedings of the Royal Society B: Biological Sciences, 277(1682), 809-817. doi:10.1098/rspb.2009.1247Martínez, F., Sardanyés, J., Elena, S. F., & Daròs, J.-A. (2011). Dynamics of a Plant RNA Virus Intracellular Accumulation: Stamping Machine vs. Geometric Replication. Genetics, 188(3), 637-646. doi:10.1534/genetics.111.129114Denhardt, D. T., & Silver, R. B. (1966). An analysis of the clone size distribution of ΦX174 mutants and recombinants. Virology, 30(1), 10-19. doi:10.1016/s0042-6822(66)81004-8Luria, S. E. (1951). THE FREQUENCY DISTRIBUTION OF SPONTANEOUS BACTERIOPHAGE MUTANTS AS EVIDENCE FOR THE EXPONENTIAL RATE OF PHAGE REPRODUCTION. Cold Spring Harbor Symposia on Quantitative Biology, 16(0), 463-470. doi:10.1101/sqb.1951.016.01.033Chao, L., Rang, C. U., & Wong, L. E. (2002). Distribution of Spontaneous Mutants and Inferences about the Replication Mode of the RNA Bacteriophage  6. Journal of Virology, 76(7), 3276-3281. doi:10.1128/jvi.76.7.3276-3281.2002Marro, J., & Dickman, R. (1999). Nonequilibrium Phase Transitions in Lattice Models. doi:10.1017/cbo9780511524288Elena, S. F., Carrasco, P., Daròs, J.-A., & Sanjuán, R. (2006). Mechanisms of genetic robustness in RNA viruses. EMBO reports, 7(2), 168-173. doi:10.1038/sj.embor.7400636Jockusch, H., Wiegand, C., Mersch, B., & Rajes, D. (2001). Mutants ofTobacco mosaic viruswith Temperature-Sensitive Coat Proteins Induce Heat Shock Response in Tobacco Leaves. Molecular Plant-Microbe Interactions, 14(7), 914-917. doi:10.1094/mpmi.2001.14.7.914Tarazona, P. (1992). Error thresholds for molecular quasispecies as phase transitions: From simple landscapes to spin-glass models. Physical Review A, 45(8), 6038-6050. doi:10.1103/physreva.45.6038Saakian, D. B., Biebricher, C. K., & Hu, C.-K. (2009). Phase diagram for the Eigen quasispecies theory with a truncated fitness landscape. Physical Review E, 79(4). doi:10.1103/physreve.79.041905Sardanyés, J., & Elena, S. F. (2010). Error threshold in RNA quasispecies models with complementation. Journal of Theoretical Biology, 265(3), 278-286. doi:10.1016/j.jtbi.2010.05.018Rodrigo, G., Carrera, J., Jaramillo, A., & Elena, S. F. (2010). Optimal viral strategies for bypassing RNA silencing. Journal of The Royal Society Interface, 8(55), 257-268. doi:10.1098/rsif.2010.026

Robust nonlinear trajectory controllers for a single-rotor UAV with particle swarm optimization tuning

This paper presents the utilization of robust nonlinear control schemes for a single-rotor unmanned aerial vehicle (SR-UAV) mathematical model. The nonlinear dynamics of the vehicle are modeled according to the translational and rotational motions. The general structure is based on a translation controller connected in cascade with a P-PI attitude controller. Three different control approaches (classical PID, Super Twisting, and Adaptive Sliding Mode) are compared for the translation control. The parameters of such controllers are hard to tune by using a trial-and-error procedure, so we use an automated tuning procedure based on the Particle Swarm Optimization (PSO) method. The controllers were simulated in scenarios with wind gust disturbances, and a performance comparison was made between the different controllers with and without optimized gains. The results show a significant improvement in the performance of the PSO-tuned controllers.Peer ReviewedPostprint (published version

UFMylation of MRE11 is essential for telomere length maintenance and hematopoietic stem cell survival

International audienc

A new regulatory mechanism of protein phosphatase 2A activity via SET in acute myeloid leukemia

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy. Although novel emerging drugs are available, the overall prognosis remains poor and new therapeutic approaches are required. PP2A phosphatase is a key regulator of cell homeostasis and is recurrently inactivated in AML. The anticancer activity of several PP2A-activating drugs (e.g., FTY720) depends on their interaction with the SET oncoprotein, an endogenous PP2A inhibitor that is overexpressed in 30% of AML cases. Elucidation of SET regulatory mechanisms may therefore provide novel targeted therapies for SET-overexpressing AMLs. Here, we show that upregulation of protein kinase p38 beta is a common event in AML. We provide evidence that p38 beta potentiates SET-mediated PP2A inactivation by two mechanisms: facilitating SET cytoplasmic translocation through CK2 phosphorylation, and directly binding to and stabilizing the SET protein. We demonstrate the importance of this new regulatory mechanism in primary AML cells from patients and in zebrafish xenograft models. Accordingly, combination of the CK2 inhibitor CX-4945, which retains SET in the nucleus, and FTY720, which disrupts the SET-PP2A binding in the cytoplasm, significantly reduces the viability and migration of AML cells. In conclusion, we show that the p38 beta/CK2/SET axis represents a new potential therapeutic pathway in AML patients with SET-dependent PP2A inactivation

Machine Learning-Based Analysis in the Management of Iatrogenic Bile Duct Injury During Cholecystectomy: a Nationwide Multicenter Study

Background Iatrogenic bile duct injury (IBDI) is a challenging surgical complication. IBDI management can be guided by artificial intelligence models. Our study identified the factors associated with successful initial repair of IBDI and predicted the success of definitive repair based on patient risk levels. Methods This is a retrospective multi-institution cohort of patients with IBDI after cholecystectomy conducted between 1990 and 2020. We implemented a decision tree analysis to determine the factors that contribute to successful initial repair and developed a risk-scoring model based on the Comprehensive Complication Index. Results We analyzed 748 patients across 22 hospitals. Our decision tree model was 82.8% accurate in predicting the success of the initial repair. Non-type E (p < 0.01), treatment in specialized centers (p < 0.01), and surgical repair (p < 0.001) were associated with better prognosis. The risk-scoring model was 82.3% (79.0-85.3%, 95% confidence interval [CI]) and 71.7% (63.8-78.7%, 95% CI) accurate in predicting success in the development and validation cohorts, respectively. Surgical repair, successful initial repair, and repair between 2 and 6 weeks were associated with better outcomes. Discussion Machine learning algorithms for IBDI are a novel tool may help to improve the decision-making process and guide management of these patients

Understanding different dominance patterns in western Amazonian forests

Dominance of neotropical tree communities by a few species is widely documented, but dominant trees show a variety of distributional patterns still poorly understood. Here, we used 503 forest inventory plots (93,719 individuals ≥2.5 cm diameter, 2609 species) to explore the relationships between local abundance, regional frequency and spatial aggregation of dominant species in four main habitat types in western Amazonia. Although the abundance-occupancy relationship is positive for the full dataset, we found that among dominant Amazonian tree species, there is a strong negative relationship between local abundance and regional frequency and/or spatial aggregation across habitat types. Our findings suggest an ecological trade-off whereby dominant species can be locally abundant (local dominants) or regionally widespread (widespread dominants), but rarely both (oligarchs). Given the importance of dominant species as drivers of diversity and ecosystem functioning, unravelling different dominance patterns is a research priority to direct conservation efforts in Amazonian forests.Publisher PDFPeer reviewe

Sex-related differences in aging rate are associated with sex chromosome system in amphibians

Sex-related differences in mortality are widespread in the animal kingdom. Although studies have shown that sex determination systems might drive lifespan evolution, sex chromosome influence on aging rates have not been investigated so far, likely due to an apparent lack of demographic data from clades including both XY (with heterogametic males) and ZW (heterogametic females) systems. Taking advantage of a unique collection of capture-recapture datasets in amphibians, a vertebrate group where XY and ZW systems have repeatedly evolved over the past 200 million years, we examined whether sex heterogamy can predict sex differences in aging rates and lifespans. We showed that the strength and direction of sex differences in aging rates (and not lifespan) differ between XY and ZW systems. Sex-specific variation in aging rates was moderate within each system, but aging rates tended to be consistently higher in the heterogametic sex. This led to small but detectable effects of sex chromosome system on sex differences in aging rates in our models. Although preliminary, our results suggest that exposed recessive deleterious mutations on the X/Z chromosome (the "unguarded X/Z effect") or repeat-rich Y/W chromosome (the "toxic Y/W effect") could accelerate aging in the heterogametic sex in some vertebrate clades.Peer reviewe

Crop pests and predators exhibit inconsistent responses to surrounding landscape composition

The idea that noncrop habitat enhances pest control and represents a win–win opportunity to conserve biodiversity and bolster yields has emerged as an agroecological paradigm. However, while noncrop habitat in landscapes surrounding farms sometimes benefits pest predators, natural enemy responses remain heterogeneous across studies and effects on pests are inconclusive. The observed heterogeneity in species responses to noncrop habitat may be biological in origin or could result from variation in how habitat and biocontrol are measured. Here, we use a pest-control database encompassing 132 studies and 6,759 sites worldwide to model natural enemy and pest abundances, predation rates, and crop damage as a function of landscape composition. Our results showed that although landscape composition explained significant variation within studies, pest and enemy abundances, predation rates, crop damage, and yields each exhibited different responses across studies, sometimes increasing and sometimes decreasing in landscapes with more noncrop habitat but overall showing no consistent trend. Thus, models that used landscape-composition variables to predict pest-control dynamics demonstrated little potential to explain variation across studies, though prediction did improve when comparing studies with similar crop and landscape features. Overall, our work shows that surrounding noncrop habitat does not consistently improve pest management, meaning habitat conservation may bolster production in some systems and depress yields in others. Future efforts to develop tools that inform farmers when habitat conservation truly represents a win–win would benefit from increased understanding of how landscape effects are modulated by local farm management and the biology of pests and their enemies

Crop pests and predators exhibit inconsistent responses to surrounding landscape composition

The idea that noncrop habitat enhances pest control and represents a win–win opportunity to conserve biodiversity and bolster yields has emerged as an agroecological paradigm. However, while noncrop habitat in landscapes surrounding farms sometimes benefits pest predators, natural enemy responses remain heterogeneous across studies and effects on pests are inconclusive. The observed heterogeneity in species responses to noncrop habitat may be biological in origin or could result from variation in how habitat and biocontrol are measured. Here, we use a pest-control database encompassing 132 studies and 6,759 sites worldwide to model natural enemy and pest abundances, predation rates, and crop damage as a function of landscape composition. Our results showed that although landscape composition explained significant variation within studies, pest and enemy abundances, predation rates, crop damage, and yields each exhibited different responses across studies, sometimes increasing and sometimes decreasing in landscapes with more noncrop habitat but overall showing no consistent trend. Thus, models that used landscape-composition variables to predict pest-control dynamics demonstrated little potential to explain variation across studies, though prediction did improve when comparing studies with similar crop and landscape features. Overall, our work shows that surrounding noncrop habitat does not consistently improve pest management, meaning habitat conservation may bolster production in some systems and depress yields in others. Future efforts to develop tools that inform farmers when habitat conservation truly represents a win–win would benefit from increased understanding of how landscape effects are modulated by local farm management and the biology of pests and their enemies